Intracellular degradation of newly synthesized apolipoprotein B.

Intracellular degradation of newly synthesized apolipoprotein (apo) B can occur at every stage of the secretory pathway, from the protein translation, polypeptide translocation across the membrane of endoplasmic reticulum (ER), to vesicular transport. The prevalence of apoB degradation at each stage varies in different hepatic cell systems examined. Proteolysis of nascent apoB can be catalyzed by the ubiquitin-proteasome system in the cytosol, and probably by unidentified ER resident proteases as well. Cytosolic and ER lumenal molecular chaperones that facilitate apoB translocation and folding may also assist in the degradation of misfolded apoB proteins. Factors affecting the synthesis and mobilization of lipids during lipoprotein assembly exert important regulatory effects on apoB degradation in trans, and specific hydrophobic amino acid sequence elements within the apoB-100 molecule may play roles in apoB degradation in cis. This review summarizes the current understanding of the cellular and molecular mechanisms responsible for intracellular degradation of apoB in hepatocytes. The emphasis centers primarily on the topology of apoB with respect to the ER membrane during and after apoB translation and its relationship to proteolytic mechanisms potentially involved in apoB degradation.